TRPM7-deficiëntie beschermt tegen myocardiale ischemie-reperfusieschade

BACKGROUND:Ischemic heart disease is one of the leading causes of death worldwide. Timely reperfusion is necessary for myocardium salvage but triggers paradoxical cardiomyocyte death and contributes to up to 50% of the final infarct size, known as lethal ischemia/reperfusion (I/R) injury. TRPM7 (transient receptor potential melastatin 7) is a divalent cation–permeable, nonselective channel kinase that can sense oxidative stress and release Zn2+from unique intracellular TRPM7 vesicles. However, the pathophysiological role of intracellular TRPM7 remains poorly understood.METHODS:TRPM7 expression was determined in hearts from patients with ischemic heart failure and I/R-injured mice. Global cardiomyocyte-specific (cmTrpm7−/−) and fibroblast-specific (fibTrpm7−/−)Trpm7knockout mice were used to determine the role of TRPM7 in I/R injury. Mechanistic investigations were conducted in primary neonatal mouse cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes with patc